A system composed by solid lipid nanoparticles (SLN) entrapped into a chemical hydrogel of dextran was recently proposed for the controlled release of lipophilic drugs in oral formulations. This study reports now an extension of such study focused on the investigation of how the nature and the amount of the formulation components are able to modify the properties of the system. In particular the concentration of the two surfactants used for the nanosuspension stabilization, the nature of the lipid phase used for the nanoparticles preparation, as well as the concentration and the derivatization degree of the polymer employed for the gel preparation were investigated. The effects of these variables on the physicochemical properties of the nanoparticles and/or on the release profiles of the model drug (S)-(+)- 2-(4- isobutylphenyl)-propionic acid (ibuprofen) were reported and discussed. Rheological experiments on samples of SLN, dextran hydrogel, and SLN-dextran hydrogel were also performed.